Psoriasis is a chronic inflammatory dermatosis that affects about 2% of the Caucasian population. It is characterized by hyperproliferation of epidermal cells and inflammation resulting from infiltration of activated T-helper cells and mononuclear cells and release of pro-inflammatory cytokines (Menter and Barker, Lancet 338:231, 1991; Barker, Lancet 338:227, 1991). It may also be associated with arthritis and can present as a severely inflammatory dermatosis in patients with acquired immunodeficiency syndrome (AIDS) (Duvic, J. Invest. Dermatol. 95:385, 1990). The symptoms of psoriasis include sharply defined erythematous patches covered with a distinctive scale, hyperproliferation of the epidermis, incomplete differentiation of keratinocytes and dermal inflammation. Clinical variants of psoriasis include erythroderma, seborrheic, inverse, guttate, and photosensitive psoriasis, pustular variants and Reiter's disease.
The role of immunomodulation in psoriasis is supported by the pharmacological action of drugs such as cyclosporine. For example, inhibition of the synthesis of interleukin-2 prevents the proliferation of T-cells and thus their release of cytokines. Mediators of inflammation play a role in the immunoregulation of psoriasis. Currently available methods for treatment include topical therapy, phototherapy, photochemotherapy and systemic therapy and provide, at best, only temporary relief. Topical glucocorticoids are most commonly prescribed as the initial treatment of psoriasis for their anti-inflammatory, antimitotic and antipruritic effects. However, their efficacy is often short term. Crude coal tar is a complex mixture of thousands of hydrocarbon compounds and affects psoriasis by enzyme inhibition and antimitotic action. Although effective, tar stains the skin and has an odor. Anthralin (dithranol) is used topically and inhibits enzyme metabolism and reduces epidermal mitotic turnover. Remission may last for weeks to months. Phototherapy and photochemotherapy entailing the administration of the photosensitizing drug methoxsalen are only temporarily effective, as psoriasis recurs months after this treatment is discontinued. This recurrence indicates that the therapy is palliative rather than curative. Long-term consequences are altered immunologic effects and an increased risk of carcinogenesis.
Methotrexate is the most commonly administered systemic cytotoxic agent for widespread psoriasis. Contraindications are numerous and after withdrawal, psoriatic symptoms may be more severe than during earlier episodes. Hydroxyurea, etretinate, cyclosporine, and AZT are also systemic medications used for the control of psoriasis and all have serious side effects. Clearly, an understanding of the pathogenesis of psoriasis remains an important challenge in dermatologic medical treatment.
Associations between psoriasis and certain human lymphocyte antigen (HLA) alleles have been described. This factor has been used to support the hypothesis that psoriasis is a T-cell-mediated, autoimmune disorder (Bos, Br. J. Dermatol. 118:141, 1988; Baadsgaard et al., Proc. Nat. Acad. Sci. USA 87:4256, 1990; Ortonne, Br. J. Dermatol. 140:1, 1999). The presence of the HLA-Cw6 allele may predispose to psoriasis because there is a strong association between age of onset, family history, and the presence of HLA-Cw6, B-13 and B-w-57 (Henseler and Christophers, J. Am. Acad. Dermatol. 13:450, 1985; Christophers and Henseler, Acta Dermato-Venereol. Suppl., 151:88, 1989; Elder et al., Arch. Dermatol. 130:216, 1994). The relative risk of HLA-Cw6 carriers developing psoriasis is 20 (Talkainen et al., Br. J. Dermatol. 192:179 1980). This association between psoriasis and HLA indicates that certain HLA alleles are more frequent in psoriasis patients than in controls. Loci are “linked” when they do not assort independently at meiosis.
Monozygotic twins have significantly higher concordance rates of disease generally than dizygotic twins (Brandrup et al., Arch. Dermatol. 114:874, 1978; Watson et al., Arch. Dermatol. 105:197, 1972). Psoriasis has also been reported to aggregate in some families (Pietrzyk et al., Arch. Dermatol. Res. 273:295, 1982; Karvonen et al., Ann. Clin. Res. 8:298, 1976; Civatte et al., Ann. Dermatol. Venereol. 104:525, 1977; Espinoza et al., J. Rheumatol. 7:445, 1980). The aggregation of psoriasis in families suggests that psoriasis can be inherited as an autosomal dominant trait with penetrance values of 10 to 50%. About 30% of psoriasis patients have a first degree relative with the disease (Barker, 1991, supra).
A need continues to exist in the medical arts for preparations and techniques for both diagnosing and treating psoriasis and psoriasis-like conditions that have less severe side effects and are more effective in treating the source of the disease. The present invention is directed to compositions, including polynucleotides, polypeptides and antibodies, and methods useful for the diagnosis of psoriasis and/or the amelioration of the symptoms of psoriasis.